Pazocent is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). Pazocent is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. The efficacy of Pazocent for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated.
Pazopanib is a multi-tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR 2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α and -β, fibroblast growth factor receptor (FGFR)-1 and -3, cytokine receptor (Kit), interleukin-2 receptor-inducible T-cell kinase (Itk), lymphocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In vitro, Pazopanib inhibited ligand-induced autophosphorylation of VEGFR-2, Kit, and PDGFR-β receptors. Absorption : Pazopanib is absorbed orally with median time to achieve peak concentrations of 2 to 4 hours after the dose. Daily dosing at 800 mg results in geometric mean AUC and C max of 1,037 mcg/mL and 58.1 mcg/mL (equivalent to 132 µM), respectively. There was no consistent increase in AUC or C max at Pazopanib doses above 800 mg. Distribution : Binding of Pazopanib to human plasma protein in vivo was greater than 99% with no concentration dependence over the range of 10 to 100 mcg/mL. In vitro, studies suggest that Pazopanib is a substrate for P-gp and BCRP. Metabolism : In vitro studies demonstrated that Pazopanib is metabolized by CYP3A4 with a minor contribution from CYP1A2 and CYP2C8. Elimination : Pazopanib has a mean half-life of 30.9 hours after administration of the recommended dose of 800 mg. Elimination is primarily via feces with renal elimination accounting for less than 4% of the administered dose.
Always consult a registered doctor before taking any medicine. This information is for general knowledge only.
The recommended starting dose of Pazopanib is 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). The dose of Pazopanib should not exceed 800 mg. Tablets should not be crushed due to the potential for increased rate of absorption which may affect systemic exposure. If a dose is missed, it should not be taken if it is less than 12 hours until the next dose. Or, as directed by the registered physicians.
Common side effects of Pazocent include: Hepatic Toxicity and Hepatic Impairment QT Prolongation and Torsades de Pointes Cardiac Dysfunction Hemorrhagic Events Arterial and Venous Thromboembolic Events Thrombotic Microangiopathy Gastrointestinal Perforation and Fistula Interstitial Lung Disease/Pneumonitis Reversible Posterior Leukoencephalopathy Syndrome Hypertension Hypothyroidism Proteinuria Tumor Lysis Syndrome Infection Increased Toxicity with Other Cancer Therapy
It is contraindicated in patients with known hypersensitivity to Pazopanib or any other components of this product.
Drugs that Inhibit or Induce Cytochrome P450 3A4 Enzymes : In vitro studies suggested that the oxidative metabolism of Pazocent in human liver microsomes is mediated primarily by CYP3A4, with minor contributions from CYP1A2 and CYP2C8. Therefore, inhibitors and inducers of CYP3A4 may alter the metabolism of Pazocent. CYP3A4 Inhibitors : Coadministration of Pazocent with strong inhibitors of CYP3A4 (e.g., Ketoconazole, Ritonavir, Clarithromycin) increases Pazocent concentrations and should be avoided. Consider an alternate concomitant medication with no or minimal potential to inhibit CYP3A4. If coadministration of a strong CYP3A4 inhibitor is warranted, reduce the dose of Pazocent to 400 mg. Grapefruit or grapefruit juice should be avoided as it inhibits CYP3A4 activity and may also increase plasma concentrations of Pazocent. CYP3A4 Inducers : CYP3A4 inducers, such as Rifampin, may decrease plasma Pazocent concentrations. Consider an alternate concomitant medication with no or minimal enzyme induction potential. Pazocent should not be used if chronic use of strong CYP3A4 inducers cannot be avoided. Drugs that Inhibit Transporters : In vitro studies suggested that Pazocent is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Therefore, absorption and subsequent elimination of Pazocent may be influenced by products that affect P-gp and BCRP. Concomitant treatment with strong inhibitors of P-gp or BCRP should be avoided due to risk of increased exposure to Pazocent. Selection of alternative concomitant medicinal products with no or minimal potential to inhibit P-gp or BCRP should be considered. Effects of Pazocent on CYP Substrates : Results from drug-drug interaction trials conducted in cancer patients suggest that Pazocent is a weak inhibitor of CYP3A4, CYP2C8, and CYP2D6 in vivo, but had no effect on CYP1A2, CYP2C9, or CYP2C19. Concomitant use of Pazocent with agents with narrow therapeutic windows that are metabolized by CYP3A4, CYP2D6, or CYP2C8 is not recommended. Coadministration may result in inhibition of the metabolism of these products and create the potential for serious adverse events. Effect of Concomitant Use of Pazocent and Simvastatin : Concomitant use of Pazocent and Simvastatin increases the incidence of ALT elevations. Across monotherapy trials with Pazocent, ALT greater than 3 x ULN was reported in 126/895 (14%) of patients who did not use statins, compared with 11/41 (27%) of patients who had concomitant use of Simvastatin. If a patient receiving concomitant Simvastatin develops ALT elevations, follow dosing guidelines for Pazocent or consider alternatives to Pazocent. Alternatively, consider discontinuing Simvastatin. Insufficient data are available to assess the risk of concomitant administration of alternative statins and Pazocent.
Hepatic Toxicity and Hepatic Impairment : In clinical trials with Pazocent, hepatotoxicity, manifested as increases in serum transaminases (alanine transferase [ALT], aspartate aminotransferase [AST]) and bilirubin, was observed. This hepatotoxicity can be severe and fatal. Patients older than 65 years are at greater risk for hepatotoxicity. Transaminase elevations occur early in the course of treatment (92.5% of all transaminase elevations of any grade occurred in the first 18 weeks). QT Prolongation and Torsades De Pointes : In the RCC trials of Pazocent, QT prolongation (greater than or equal to 500 msec) was identified on routine electrocardiogram (ECG) monitoring in 2% (11/558) of patients. Torsades de pointes occurred in less than 1% (2/977) of patients who received Pazocent in the monotherapy trials. Pazocent should be used with caution in patients with a history of QT interval prolongation, in patients taking antiarrhythmics or other medications that may prolong QT interval, and those with relevant pre-existing cardiac disease. When using Pazocent, baseline and periodic monitoring of ECGs and maintenance of electrolytes (e.g., calcium, magnesium, potassium) within the normal range should be performed.